ABSTRACT (Biomedical Research) Research Project 1 Project 1 is one of two Biomedical Research (BMR) Projects for the proposed ?Center for Environmental and Health Effects of PFAS? being led by North Carolina State University (NC State). Per- and polyfluoroalkyl substances (PFAS) are common drinking water contaminants in NC and around the United States. Little is known about how long these chemicals stay in the body or what the human health impacts are. These chemicals have been detected in the drinking water of communities living along the Cape Fear River in NC. Working with three community groups along the Cape Fear River, we will evaluate PFAS exposure and thyroid health effects to people whose drinking water has been contaminated with PFAS. Disruption of thyroid hormones as well as metabolic outcomes such as obesity have been associated with PFAS in other populations. The three communities have exposure to different types of PFAS in their drinking water. Pittsboro, located on the Haw River in the upper region of the Cape Fear River basin, is exposed to historically used PFAS as a result of upstream use of firefighting foam, wastewater discharges, and land application of biosolids. The Fayetteville private well community is located near a fluorochemical plant that discharged PFAS to both air and water (Cape Fear River) since 1980; their wells are believed to be contaminated as a result of air transport. Wilmington, at the mouth of the Cape Fear River and downstream of the chemical plant, is exposed to both historically used PFAS (e.g., PFOA, PFOS) as well as a number of newly identified PFAS (e.g., GenX, Nafion byproduct 2). To study these diverse communities, we plan to recruit 1,200 individuals in the region (300 from Pittsboro, 200 from the Fayetteville private well community, and 700 from Wilmington) to evaluate how PFAS levels change over time, whether personal characteristics influence PFAS level as well as excretion from the body, and whether PFAS, either individually or as a group, influence thyroid outcomes. We plan to include individuals ages 6 and over who have lived in the region since July 2016. We will invite participants to clinic visits in Years 1 and 3 to collect blood and urine samples for PFAS and clinical analyses, administer questionnaires to obtain information on water use history, demographic characteristics, and medical and health outcomes. Working with our community partners, we will report back individual and community-level results on a regular basis. We will have Community Science Advisory Boards in each community to provide input to the study and ensure that the study investigators are well informed about community concerns. We anticipate finding PFAS mixtures in each community; we will use statistical approaches that allow us to evaluate individual PFAS while taking into account the complex mixture present. This study, with its complex mix of PFAS and racially diverse sample, will provide key insights to the human health implications of PFAS both in NC and around the world.